Zinc is essential for human health. Marginal deficiency of zinc appears to be widespread but the diagnostic criteria for this have not been developed. Sites of zinc absorption and homeostatic control mechanisms at the gastro-intestinal tract level during zinc deficiency and sufficiency are not well characterized in human subjects. The specific aims of this project are to determine homeostatic control mechanisms of zinc and define marginal zinc deficiency in human subjects. These objectives will be accomplished by experimentally inducing a marginal specific deficiency of zinc in adult volunteers followed by appropriate repletion phases. The parameters of measurement will be: zinc absorption and plasma appearance kinetics using the novel method of stable isotopes and neutron activation analysis; zinc balance, zinc concentration in plasma, red cells, neutrophils, lymphocytes, hair, sweat, and saliva; assay of selected zinc dependent enzymes in the plasma, red cells, and neutrophils, dark adaptation, serum vitamin A and retinol binding protein; serum fatty acids, cholesterol, HDL, LDL, and lymphocyte function tests. A semi-purified diet based on texturized soy protein with different levels of zinc will be used for our study. All other macro and micro-nutrients will be supplied according to RDA. Throughout the experiment, the diet will remain constant except for zinc (5 mg/day during zinc restricted or depletion phase and 30 mg/day during zinc repletion phase). Zinc depletion phase will follow appropriate stabilization period as outlined in the proposal. Alkaline phosphatase, in the plasma, phosphorylase and adenosien deaminase in the red cells, alkaline phosphatase in the neutrophils (quantitative), and nucleoside phosphorylase and adenosine deaminase in the lymphocytes, will be determined and correlated with changes in zinc levels due to dietary manipulation. In vitro assessments of lymphocyte functional activity will also be made. During the progression of depletion-repletion phases for zinc, appropriate measurements of gastro-intestinal absorption, zinc balance, endogenous secretion and plasma appearance kinetics of stable isotopes of zinc will be carried out. Thus, these studies will provide us with sensitive criteria for making a diagnosis of marginal zinc deficiency and will provide homeostatic control mechanism of zinc at the gatro-intestinal level.